I biologici sono proteine ​​prodotte che interrompono il processo immunitario coinvolto nella psoriasi. A differenza delle terapie mediche immunosoppressive generalizzate come il metotrexato, i biologici prendono di mira aspetti specifici del sistema immunitario che contribuiscono alla psoriasi.(84) These medications are generally well tolerated, and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis.(84)(86) However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.(84)

Guidelines regard biologics as third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments.(86) The safety of biologics during pregnancy has not been assessed. European guidelines recommend avoiding biologics if a pregnancy is planned; anti-TNF therapies such as infliximab are not recommended for use in chronic carriers of the hepatitis B virus or individuals infected with HIV.(84)

Several monoclonal antibodies target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF-α is one of the main executor inflammatory cytokines. Four monoclonal antibodies (MAbs) (infliximab, adalimumab, golimumab, and certolizumab pegol) and one recombinant TNF-α decoy receptor, etanercept, have been developed to inhibit TNF-α signaling. Additional monoclonal antibodies, such as ixekizumab,(87) have been developed against pro-inflammatory cytokines(88) and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies.(31) IL-12 and IL-23 share a common domain, p40, which is the target of the FDA-approved ustekinumab.(33) In 2017 the US FDA approved guselkumab for plaque psoriasis.(89) There have been few studies of the efficacy of anti-TNF medications for psoriasis in children. One randomized control study suggested that 12 weeks of etanercept treatment reduced the extent of psoriasis in children with no lasting adverse effects.(90)

Two medications that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal antibody that specifically targets the CD11a subunit of LFA-1.(84) It also blocks the adhesion molecules on the endothelial cells that line blood vessels, which attract T cells. Efalizumab was voluntarily withdrawn from the European market in February 2009, and from the U.S. market in June 2009, by the manufacturer due to the medication's association with cases of progressive multifocal leukoencephalopathy.(84) Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causes natural killer cells to kill T cells as a way of controlling inflammation.(31) Apremilast may also be used.(12)

Individuals with psoriasis may develop neutralizing antibodies against monoclonal antibodies. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody such as infliximab from binding antigen in a laboratory test. Specifically, neutralization occurs when the antidrug antibody binds to infliximab's antigen binding site instead of TNF-α. When infliximab no longer binds tumor necrosis factor alpha, it no longer decreases inflammation, and psoriasis may worsen. Neutralizing antibodies have not been reported against etanercept, a biologic medication that is a fusion protein composed of two TNF-α receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor, and the development of immune tolerance.(91)

A 2020 meta-analysis found that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab were the most effective biologics for treating psoriasis.(92)(93) In general, anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha biologics were found to be more effective than traditional systemic treatments.(92) The immunologic pathways of psoriasis involve Th9, Th17, Th1 lymphocytes, and IL-22. The aforementioned biologic agents hinder different aspects of these pathways.(citation needed)

Another treatment for moderate to severe psoriasis is fumaric acid esters (FAE) which may be similar in effectiveness to methotrexate.(94)

It has been theorized that antistreptococcal medications may improve guttate and chronic plaque psoriasis; however the limited studies do not show that antibiotics are effective.(95)

Chirurgia(edit)

Limited evidence suggests removal of the tonsils may benefit people with chronic plaque psoriasis, guttate psoriasis, and palmoplantar pustulosis.(96)(97)

Diet(edit)

Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).(98) A low-calorie diet appears to improve the severity of psoriasis.(38) Diet recommendations include consumption of cold water fish (preferably wild fish, not farmed) such as salmon, herring, and mackerel; extra virgin olive oil; legumes; vegetables; fruits; and whole grains; and avoid consumption of alcohol, red meat, and dairy products (due to their saturated fat). The effect of consumption of caffeine (including coffee, black tea, mate, and dark chocolate) remains to be determined.(99)

There is a higher rate of celiac disease among people with psoriasis.(99)(100) When adopting a gluten-free diet, disease severity generally decreases in people with celiac disease and those with anti-gliadin antibodies.(98)(101)(102)

Prognosi(edit)

Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies.(69)

Psoriasis is known to have a negative impact on the quality of life of both the affected person and the individual's family members.(33) Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Itching and pain can interfere with basic functions, such as self-care and sleep.(48) Participation in sporting activities, certain occupations, and caring for family members can become difficult activities for those with plaques located on their hands and feet.(48) Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken for dandruff.(103)

Individuals with psoriasis may feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psoriasis has been associated with low self-esteem and depression is more common among those with the condition.(3) People with psoriasis often feel prejudiced against due to the commonly held incorrect belief that psoriasis is contagious.(48) Psychological distress can lead to significant depression and social isolation; a high rate of thoughts about suicide has been associated with psoriasis.(20) Many tools exist to measure the quality of life of people with psoriasis and other dermatological disorders. Clinical research has indicated individuals often experience a diminished quality of life.(104) Children with psoriasis may encounter bullying.(105)

Several conditions are associated with psoriasis. These occur more frequently in older people. Nearly half of individuals with psoriasis over the age of 65 have at least three comorbidities (concurrent conditions), and two-thirds have at least two comorbidities.(106)

Malattia cardiovascolare(edit)

Psoriasis has been associated with obesity(3) and several other cardiovascular and metabolic disturbances. The number of new cases per year of diabetes is 27% higher in people affected by psoriasis than in those without the condition.(107) Severe psoriasis may be even more strongly associated with the development of diabetes than mild psoriasis.(107) Younger people with psoriasis may also be at increased risk for developing diabetes.(106)(108) Individuals with psoriasis or psoriatic arthritis have a slightly higher risk of heart disease and heart attacks when compared to the general population. Cardiovascular disease risk appeared to be correlated with the severity of psoriasis and its duration. There is no strong evidence to suggest that psoriasis is associated with an increased risk of death from cardiovascular events. Methotrexate may provide a degree of protection for the heart.(37)(106)

The odds of having hypertension are 1.58 times higher in people with psoriasis than those without the condition; these odds are even higher with severe cases of psoriasis. A similar association was noted in people who have psoriatic arthritis—the odds of having hypertension were found to be 2.07 times greater when compared to odds of the general population. The link between psoriasis and hypertension is not currently(quando?) inteso. Mechanisms hypothesized to be involved in this relationship include the following: dysregulation of the renin–angiotensin system, elevated levels of endothelin 1 in the blood, and increased oxidative stress.(108)(109) The number of new cases of the heart rhythm abnormality atrial fibrillation is 1.31 times higher in people with mild psoriasis and 1.63 times higher in people with severe psoriasis.(110) There may be a slightly increased risk of stroke associated with psoriasis, especially in severe cases.(37)(111) Treating high levels of cholesterol with statins has been associated with decreased psoriasis severity, as measured by PASI score, and has also been associated with improvements in other cardiovascular disease risk factors such as markers of inflammation.(112) These cardioprotective effects are attributed to ability of statins to improve blood lipid profile and because of their anti-inflammatory effects. Statin use in those with psoriasis and hyperlipidemia was associated with decreased levels of high-sensitivity C-reactive protein and TNFα as well as decreased activity of the immune protein LFA-1.(112) Compared to individuals without psoriasis, those affected by psoriasis are more likely to satisfy the criteria for metabolic syndrome.(16)(110)

Other diseases(edit)

The rates of Crohn disease and ulcerative colitis are increased when compared with the general population, by a factor of 3.8 and 7.5 respectively.(3) People with psoriasis also have a higher risk of celiac disease.(99)(102) Few studies have evaluated the association of multiple sclerosis with psoriasis, and the relationship has been questioned.(3)(113) Psoriasis has been associated with a 16% increase in overall relative risk for non-skin cancer.(37) People with psoriasis have a 52% increased risk cancers of the lung and bronchus, a 205% increase in the risk of developing cancers of the upper gastrointestinal tract, a 31% increase in the risk of developing cancers of the urinary tract, a 90% increase in the risk of developing liver cancer, and a 46% increase in the risk of developing pancreatic cancer.(37) The risk for development of non-melanoma skin cancers is also increased. Psoriasis increases the risk of developing squamous cell carcinoma of the skin by 431% and increases the risk of basal cell carcinoma by 100%.(37) There is no increased risk of melanoma associated with psoriasis.(37) People with psoriasis have a higher risk of developing cancer.(114)

Epidemiology(edit)

Psoriasis is estimated to affect 2–4% of the population of the western world.(8) The rate of psoriasis varies according to age, region and ethnicity; a combination of environmental and genetic factors is thought to be responsible for these differences.(8) It can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years. Approximately one third of people with psoriasis report being diagnosed before age 20.(115) Psoriasis affects both sexes equally.(59)

Psoriasis affects about 6.7million Americans and occurs more frequently in adults.(5)

Psoriasis is about five times more common in people of European descent than in people of Asian descent. (116)

People with inflammatory bowel disease such as Crohn disease or ulcerative colitis are at an increased risk of developing psoriasis.(45) Psoriasis is more common in countries farther from the equator.(45) Persons of white European ancestry are more likely to have psoriasis and the condition is relatively uncommon in African Americans and extremely uncommon in Native Americans.(46)

History(edit)

Scholars believe psoriasis to have been included among the various skin conditions called tzaraath (translated as leprosy) in the Hebrew Bible, a condition imposed as a punishment for slander. The person was deemed “impure” (see tumah and taharah) during their afflicted phase and is ultimately treated by the kohen.(117) However, it is more likely that this confusion arose from the use of the same Greek term for both conditions. The Greeks used the term lepra (λεπρα) for scaly skin conditions. They used the term psora to describe itchy skin conditions.(117) It became known as Willan's lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases. Leprosy, they said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories: leprosa graecorum e psora leprosa.(118)

Psoriasis is thought to have first been described in Ancient Rome by Cornelius Celsus.(119) The British dermatologist Thomas Bateman described a possible link between psoriasis and arthritic symptoms in 1813.(119)

The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. In the 18th and 19th centuries, Fowler's solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis.(117) Mercury was also used for psoriasis treatment during this time period.(117) Sulfur, iodine, and phenol were also commonly used treatments for psoriasis during this era when it was incorrectly believed that psoriasis was an infectious disease.(117) Coal tars were widely used with ultraviolet light irradiation as a topical treatment approach in the early 1900s.(117)(120) During the same time period, psoriatic arthritis cases were treated with intravenously administered gold preparations in the same manner as rheumatoid arthritis.(120)

Etymology(edit)

Society and culture(edit)

The International Federation of Psoriasis Associations (IFPA) is the global umbrella organization for national and regional psoriasis associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years.(122) The Psoriasis International Network, a program of the Fondation René Touraine, gathers dermatologists, rheumatologists and other caregivers involved in the management of psoriasis.
Non-profit organizations the National Psoriasis Foundation in the United States, the Psoriasis Association in the United Kingdom and Psoriasis Australia offer advocacy and education about psoriasis in their respective countries.

Costo(edit)

The annual cost for treating psoriasis in the United States is estimated as high as $32.5billion, including $12.2billion in direct costs. Pharmacy costs are the main source of direct expense, with biologic therapy the most prevalent. These costs increase significantly when co-morbid conditions such as heart disease, hypertension, diabetes, lung disease and psychiatric disorders are factored in. Expenses linked to co-morbidities are estimated at an additional $23,000 per person per year.(123)

Ricerca(edit)

The role of insulin resistance in the pathogenesis of psoriasis is under investigation. Preliminary research has suggested that antioxidants such as polyphenols may have beneficial effects on the inflammation characteristic of psoriasis.(124)

Many novel medications being researched(quando?) target the Th17/IL-23 axis,(124) particularly IL-23p19 inhibitors, as IL-23p19 is present in increased concentrations in psoriasis skin lesions while contributing less to protection against opportunistic infections.(125) Other cytokines such as IL-17 and IL-22 also have been targets for inhibition as they play important roles in the pathogenesis of psoriasis.(125) Another avenue of research has focused on the use of vascular endothelial growth factor inhibitors to treat psoriasis.(61) Oral agents being investigated(quando?) as alternatives to medications administered by injection include Janus kinase inhibitors, protein kinase C inhibitors, mitogen-activated protein kinase inhibitors, and phosphodiesterase 4 inhibitors, all of which have proven effective in various phase 2 and 3 clinical trials.(124)(125) These agents have potentially severe side-effects due to their immunosuppressive mechanisms.(125)

^ un'Bc“Questions and Answers About Psoriasis”. www.niams.nih.gov. 12 April 2017. Archived from the original on 22 April 2017. Retrieved 22 April 2017.

^ un'Bcdefgh“Questions and Answers about Psoriasis”. National Institute of Arthritis and Musculoskeletal and Skin Diseases. October 2013. Archived from the original on 8 July 2015. Retrieved 1 July 2015.